Ghada Ajabnoor

Relative metabolic stability, but disrupted circadian cortisol secretion during the fasting month of Ramadan.

Background Chronic feeding and sleep schedule disturbances are stressors that exert damaging effects on the organism. Practicing Muslims in Saudi Arabia go through strict Ramadan fasting from dawn till sunset for one month yearly. Modern era Ramadan practices in Saudi Arabia are associated with disturbed feeding and sleep patterns, namely abstaining from food and water and increasing daytime sleep, and staying awake and receiving food and water till dawn. Hypothesis Strict Ramadan practices in Saudi Arabia may influence metabolism, sleep and circadian cortisol secretion. Protocol Young, male Ramadan practitioners were evaluated before and two weeks into the Ramadan. Blood samples were collected at 9.00 am and 9.00 pm for measurements of metabolic parameters and cortisol. Saliva was collected serially during the day for cortisol determinations. Results Ramadan practitioners had relative metabolic stability or changes expected by the pattern of feeding. However, the cortisol circadian rhythm was abolished and circulating insulin levels and HOMA index were increased during this period. Discussion The flattening of the cortisol rhythm is typical of conditions associated with chronic stress or endogenous hypercortisolism and associated with insulin resistance. Conclusions Modern Ramadan practices in Saudi Arabia are associated with evening hypercortisolism and increased insulin resistance. These changes might contribute to the high prevalence of chronic stress-related conditions, such as central obesity, hypertension, metabolic syndrome and diabetes mellitus type 2, and their cardiovascular sequelae observed in the Kingdom.

Health impact of fasting in Saudi Arabia during Ramadan: association with disturbed circadian rhythm and metabolic and sleeping patterns.

Background Muslims go through strict Ramadan fasting from dawn till sunset for one month yearly. These practices are associated with disturbed feeding and sleep patterns. We recently demonstrated that, during Ramadan, circadian cortisol rhythm of Saudis is abolished, exposing these subjects to continuously increased cortisol levels. Hypothesis Secretory patterns of other hormones and metabolic parameters associated with cortisol, and insulin resistance, might be affected during Ramadan. Protocol Ramadan practitioners (18 males, 5 females; mean age ±SEM = 23.16±1.2 years) were evaluated before and two weeks into Ramadan. Blood was collected for measurements of endocrine and metabolic parameters at 9 am (±1 hour) and again twelve hours later. Results In Ramadan, glucose concentration was kept within normal range, with a significant increase in the morning. Mean morning concentration of leptin was significantly higher than pre-Ramadan values (p = 0.001), in contrast to that of adiponectin, which was significantly lower (p<0.001). These changes were associated with increased insulin resistance in morning and evening. Concentrations of hsCRP were lower during Ramadan than those during regular living conditions, however, normal circadian fluctuation was abolished (p = 0.49). Even though means of liver enzymes, total bilirubin, total protein and albumin were all decreased during Ramadan, statistically lower means were only noted for GGT, total protein, and albumin (p = 0.018, 0.002 and 0.001 respectively). Discussion Saudi Ramadan practitioners have altered adipokine patterns, typical of insulin resistance. The noted decreases of hsCRP, liver enzymes, total protein, and albumin, are most likely a result of fasting, while loss of circadian rhythmicity of hsCRP is probably due to loss of circadian cortisol rhythm. Conclusions Modern Ramadan practices in Saudi Arabia, which are associated with evening hypercortisolism, are also characterized by altered adipokines patterns, and an abolished hsCRP circadian rhythm, all likely to increase cardiometabolic risk.

Gut Microbiota: A Contributing Factor to Obesity

Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gut microbiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 1014 microorganisms reside within the lower human intestine and many of these 1014 microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition) with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review. Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics, and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity.

Effect of Ramadan fasting in Saudi Arabia on serum bone profile and immunoglobulins

Background: Each year Muslims fast from dawn to sunset for 1 month (Ramadan). In Saudi Arabia, the sleep–wake cycle during Ramadan is severely disturbed and is associated with abolition of the circadian cortisol rhythm, exposing Saudis to continuously increased cortisol levels, which may influence the immune response. In addition to cortisol, sleep and fasting affect the secretion of parathyroid hormone (PTH) and hence bone metabolism. Methods: Our objective was to investigate the effect of Ramadan type fasting on secretory patterns of PTH, markers of bone metabolism, and serum immunoglobulins. Blood samples from healthy young volunteers were collected at 9 a.m. and 9 p.m. (± 1 hour) before (Shaban) and 2 weeks into Ramadan. Calcium, phosphorus, magnesium, albumin, alkaline phosphatase, 25-OH vitamin D, intact PTH (iPTH), and immunoglobulin (Ig) A, M and G were measured. Results: During Ramadan, evening-adjusted calcium was higher (p = 0.036) and phosphate lower (p < 0.001) than the corresponding morning value. Moreover, the Ramadan mean morning phosphate was higher and the evening level lower was than Shabaan values (p = 0.010 and p <0.001, respectively), while mean iPTH level was decreased compared with the morning value (p = 0.001), and the evening mean during Shabaan (p = 0.029). Mean IgG concentration was significantly lower during Ramadan (p = 0.003 and p = 0.021 for morning and evening, respectively). Conclusions: Changes in dietary practices during Ramadan modulated PTH secretion to a pattern which might be beneficial to bone health. Combined effects of fasting and disturbed sleep led to a noted decrease in IgG level. Therefore, a possible beneficial effect of fasting on bone turnover is combined with decreased immune response.

Ramadan fasting in Saudi Arabia is associated with altered expression of CLOCK, DUSP and IL-1alpha genes, as well as changes in cardiometabolic risk factors

Background During the fasting month of Ramadan, practicing Saudis develop severe disturbances in sleeping and feeding patterns. Concomitantly, cortisol circadian rhythm is abolished, diurnal cortisol levels are elevated and circulating levels of several adipokines are altered favouring insulin resistance. Aim To examine changes in the expression of CLOCK and glucocorticoid-controlled genes, such as DUSP1 and IL-1α in Saudi adults before and during Ramadan, and to investigate possible associations with selected cardiometabolic risk factors. Methods Healthy young volunteers (5 females, 18 males; mean age +SEM = 23.2 +1.2 years) were evaluated before Ramadan and two weeks into it. Blood samples were collected at 9 am (±1 hour) and twelve hours later for determination of serum lipid profile, high sensitivity CRP (hsCRP), and adiponectin. The expression of CLOCK, DUSP1 and IL-1α was evaluated in circulating leukocytes. Results Mean levels of GGT and morning adiponectin decreased, while those of LDL-c/ HDL-c and atherogenic index (AI) increased significantly in Ramadan compared to Shabaan. There was no significant difference between morning and evening adiponectin during Ramadan, while the diurnal rhythm of hsCRP was lost. CLOCK gene expression mean was significantly higher in morning than in evening during Shabaan. Mean morning and evening DUSP1 mRNA levels showed significant increase during Ramadan compared to Shabaan, however, its diurnal rhythm was maintained. Morning IL-1α mRNA expression remained significantly higher than in the evening during Ramadan, but was markedly decreased compared to Shabaan. Discussion Ramadan fasting in Saudi Arabia is associated with improvements in some cardiometabolic risk factors, such as circulating GGT and hsCRP and leukocyte expression of IL-1α mRNA, suggesting that intermittent fasting might have a beneficial component. These benefits may be offset by the previously reported dysregulation in the circadian rhythm, excess glucocorticoid levels and action, and insulin resistance, explaining increased prevalence of cardiometabolic disorders and type 2 diabetes mellitus.

Effect of Supplementation With Chitosan on Weight, Cardiometabolic, and Other Risk Indices in Wistar Rats Fed Normal and High-Fat/High-Cholesterol Diets Ad Libitum

The aim was to investigate effect of chitosan on markers of obesity and cardiometabolic risk in rats fed normal chow (NC) or high-fat/high-cholesterol diet (HF/HCD). Forty male rats were fed NC or HF/HCD for 3 months, then divided into 4 groups: group A fed NC, group B: NC + chitosan, group C: HF/HCD, and group D: HF/HCD + chitosan. Food intake and weight were recorded, and serum glucose, lipid profile, insulin, leptin, gamma glutamyl transferase (GGT), and tumor necrosis factor α were measured at beginning and after 12 weeks. Atherogenic index (AI), low-density lipoprotein cholesterol:high-density lipoprotein cholesterol (LDL-C:HDL-C), and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. At the end of study, food intake was significantly increased in group B; mean values of triglycerides, total cholesterol, LDL-C, LDL-C:HDL-C, and AI were decreased in group B and group D; mean leptin was increased in group A and decreased in group B; and mean values of insulin, HOMA-IR, and GGT were increased in group C. The results from this study suggest that chitosan improved lipid profile, insulin sensitivity, and oxidative stress caused by HF/HCD.

The relationship of management modality in Saudi patients with type 2 diabetes to components of metabolic syndrome, γ glutamyl transferase and highly sensitive C-reactive protein

Background: The aim of this study was to investigate the relationship among management modality, glycemic control, components of metabolic syndrome (MS) and serum levels of γ glutamyl transferase (GGT) and C-reactive protein (CRP) in patients with type 2 diabetes (T2DM). Methods: Patients with T2DM, not suffering from diabetes complications, were recruited from outpatients clinics at two hospitals in Jeddah. Anthropometric measurements and blood pressure (BP) were taken. A treatment plan was recorded. Fasting blood samples were obtained to measure glucose, glycated hemoglobin (HbA1c), lipids profile, highly sensitive (hs)-CRP and GGT. Results: A total of 71 men and 82 women were recruited. Lower mean HbA1c was found in people receiving oral glucose-lowering drugs compared with those on insulin therapy (p < 0.001). Management modality had no effect on mean GGT or hs-CRP. Higher mean GGT was associated with poor glycemic control, dyslipidemia, hypertension, and abdominal obesity. GGT correlated significantly (p < 0.05) and directly with triglycerides in men (r = 0.401) and diastolic BP (r = 0.279 for men, r = 0.194, for women), but inversely with high-density lipoprotein cholesterol (HDL-C) (r = −0.298 for men, r = −0.171 for women). hs-CRP correlated with waist circumference (p < 0.05, r = 0.312, for men, r = 0.305, for women), with a higher mean being found in men with poor glycemic control (p = 0.015), in hypertensive women (p = 0.030), and in patients who were abdominally obese (p < 0.05). Conclusions: High levels of GGT and hs-CRP are associated with components of MS and poor glycemic control, hence increased cardiovascular risk. Due to their value as independent risk predictors of vascular injury, these measures should be included in routine monitoring of patients with T2DM.

Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities

The use of anti-cancer adjuvant therapy is rationalized by potentiating the efficacy, and/or protecting from major side effects of chemotherapeutics. Thymoquinone (TQ) is a naturally occurring compound with cumulative evidence of anti-cancer properties. In this study, we assessed the chemomodulatory potential of TQ to gemcitabine (GCB) against human breast adenocarcinoma (MCF-7), and ductal carcinoma (T47D) cells. TQ showed cytotoxic effects against MCF-7 and T47D with IC50’s of 64.9 ± 14 µM and 165 ± 2 µM, respectively. The IC50’s of GCB against MCF-7 and T47D were 0.9 ± 0.18 µM and 14.3 ± 2.8 µM and were significantly reduced after combination with TQ to 0.058 ± 12 µM and 2.3 ± 0.2 µM, respectively. The CI- values were indicative of synergism in MCF-7 and T47D cells (0.15 and 0.30, respectively). Further investigation showed that GCB caused significant anti-proliferative effect reflected by increasing cell population in S-phase in both cell lines. TQ potentiated GCB-induced anti-proliferative activity in both cell lines. GCB induced considerable apoptosis in T47D cell line, and TQ significantly increased GCB-induced apoptotic effects by 1.5 to 3.6 folds. Interestingly, GCB, TQ and their combination induced significant autophagic cell death in the apoptosis defected MCF-7 cells. In addition, TQ, GCB and their combination depleted breast cancer associated stem cell (CD44(+)/CD24(−)/(low)) clone within MCF-7 and T47D cells by 3.8% to 27.5%. In conclusion, TQ showed promising chemomodulatory effects to GCB against breast cancer cells via inducing apoptosis, necrosis and autophagy, in addition to depleting tumor associated resistant stem cell fraction.

Molecular designing, virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR

The somatic mutations in ATP binding cleft of the tyrosine kinase binding domain of EGFR are known to occur in 15–40% of non-small cell lung cancer (NSCLC) patients. Although first and second generation anti-EGFR inhibitors are widely used to treat these patients, their therapeutic efficacy is modest and often results in adverse effects or drug resistance. Therefore, there is a need to develop novel as well as safe anti-EGFR drugs. The rapid emergence of computational drug designing provided a great opportunity to both discover and predict the efficacy of novel EGFR inhibitors from plant sources. In the present study, we designed several chemical analogues of edible curcumin (CUCM) compound and assessed their drug likeliness, ADME and toxicity properties using a diverse range of advanced computational methods. We also have examined the structural plasticity and binding characteristics of EGFR wild-type and mutant forms (S769L and K846R) against ligand molecules like Gefitinib, native CUCM, and different CUCM analogues. Through multidimensional experimental approaches, we conclude that CUCM-36 ((1E,4Z,6E)-1-(3,4-Diphenoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-phenoxyphenyl)-1,4,6-heptatrien-3-one) is the best anti-EGFR compound with high drug-likeness, ADME properties, and low toxicity properties. CUCM-36 compound has demonstrated better affinity towards both wild-type (ΔG is −8.5 kcal/Mol) and mutant forms (V769L & K846R; ΔG for both is >−9.20 kcal/Mol) compared to natural CUCM and Gefitinib inhibitor. This study advises the future laboratory assays to develop CUCM-36 as a novel drug compound for treating EGFR positive non-small cell lung cancer patients.

Supplementation with Oligonol, Prevents Weight Gain and Improves Lipid Profile in Overweight and Obese Saudi Females

Background: Obesity is a global health problem, increasing susceptibility to Type 2 Diabetes (T2DM) and Cardiovascular Disease (CVD). Varieties of products have been proposed for treatment with varying degrees of success. Recent studies, suggested Oligonol; an optimized phenolic product mixture from Lychee Fruit Polyphenols (LFP); as such treatment in Japanese population. Objectives: We aimed to investigate the effect of oligonol on weight, insulin resistance by (HOMA-IR), lipids profile, leptin, Adiponectin, and resistin in healthy overweight and obese Saudi females. Subjects and Methods: 60 Saudi healthy overweight and obese females were enrolled in a double blind case/control study to take either Oligonol or placebo for 12 weeks without dietary or lifestyle re-strictions. Weight, height, Waist Circumference (WC), hip circumference (HC), and blood pressure were measured, and fasting blood samples of participants were taken before, and at the end of study. Total cholesterol, HDL-cholesterol, triglycerides, glucose, insulin, leptin, adiponectin, and resistin were meas-ured. LDL- cholesterol, HOMA-IR were calculated by equation. Results: 47 subjects completed the study, 25 in placebo group, and 22 in Oligonol group. No ill effects were noted in any participant. Oligonol reduced means of serum triglycerides (P=0.008), and resistin (P=0.045) significantly. In addition, no weight gain was noted in oligonol group, unlike placebo group which exhibited significant increase in mean weight (P= 0.036), WC (P=0.027), HC (P= 0.047), and leptin (P <0.001). Conclusion: Oligonol could be suggested as future hypolipidemic and weight controlling agent for overweight and obese Saudi females.